Top Kratom Researcher Discusses Potential Medical Use In Opioid Withdrawal

Chris McCurdy in his lab at the University of Mississippi School of Pharmacy. (UM photo by Kevin Bain)

Users of the medicinal plant kratom are anxiously watching their calendars as Friday, September 30 approaches–the earliest date that the DEA will place two of the plant's chemicals onto Schedule I of the U.S. Controlled Substances Act. As reported extensively, this classification will effectively criminalize the sale and use of the plant as an herbal dietary supplement.

On one hand, the DEA's position, supported by the U.S. Food and Drug Administration, is that the kratom chemicals are opioids and therefore subject to abuse and pose an imminent hazard to public safety. On the other hand, an estimated 5 million people in the U.S. use kratom medically to relieve pain, depression, anxiety and PTSD, and in recovery from dependence on alcohol or prescription opioids. Over 134,000 people have signed a petition to the White House to override the DEA's intent to ban these kratom chemicals.

Nick Wing at The Huffington Post reported Monday that and 51 U.S. congressional representatives–including 21 Republicans–have formally petitioned DEA acting administrator Chuck Rosenberg to delay placement of the kratom chemicals onto Schedule I, provide ample time for public comment, and "resolve any inconsistencies with other Federal Agencies regarding the use of kratom."

In the letter, drafted by Rep. Mark Pocan (D-Wis.-2nd) and Rep. Matt Salmon (R-Ariz.-5th), the focus was specifically on the potential for kratom to treat opioid addiction, a medical use that counters the contention by DEA and FDA that kratom or its chemicals have no known medical use.

The letter cites the work of Christopher R. McCurdy, PhD, at the University of Mississippi and Edward W. Boyer, MD at the University of Massachusetts and their work to investigate how kratom is used as a painkiller substitute for strong opioids and in recovery from opioid dependence.

The debate over kratom's medical use

I caught up with Dr. McCurdy earlier this month to discuss their work and his perspective on the DEA's notice of intent.

"For years it had been on DEA's chemicals of concern but we really didn't think there was going to be any action on it," says McCurdy. A professor of medicinal chemistry and pharmacology at the Ole Miss School of Pharmacy and their interim chair of biomolecular sciences, McCurdy's research team has been studying naturally occurring plant chemicals with effects in the brain.

"We were initially interested in finding new analgesics without addictive side effects but we got away from that." The problem was finding financial support for the studies from the National Institutes of Health (NIH), the 27 institutes and centers that comprise the nation's medical research agency.

At the time, he says that the National Institute on Drug Abuse (NIDA) didn't want to fund the work because they saw medical use of an herbal supplement as alternative and complementary medicine. So, he inquired with program officials at the NIH's arm for study of supplements, the National Center for Complementary and Alternative Medicine (NCCAM, now the National Center for Complementary and Integrative Health, NCCIH). "But they didn't want to fund it because they considered it drug abuse research," says McCurdy.

McCurdy had been well-versed in the previous work on kratom in animal models, particularly that by Hirosuto Takayama and colleagues at Chiba University in Japan. Takayama who was the first to show that mitragynine and 7-hydroxymitragynine could bind to opioid receptors in guinea pigs and mice. Together with Jessica Adkins, McCurdy and Boyer's published a 2011 review on kratom alkaloids in Current Topics in Medicinal Chemistry, considered a definitive overview of the science up through the beginning of the decade.

"But the compounds in kratom aren't particularly potent opioids like prescription opioids, morphine or fentanyl. So we started investigating its traditional use from Malaysia where people used it as an opium replacement or to wean themselves off of opium--a different type of methadone or Suboxone (buprenorphine/naloxone) maintenance therapy," says McCurdy.

They repeatedly dosed mice with morphine to get them addicted. Then they stopped giving morphine and gave mice either plain food or food with freeze-dried extracts of kratom tea. The kratom tea extract almost completely blocked the morphine withdrawal symptoms.

In the meantime, they tried to standardize a kratom product and develop it. While the 7-hydroxy compound is more potent than mitragynine, it's present in very low concentrations, or not at all. McCurdy says, "We were always concerned about the 7-hydroxymitragynine and were even trying to get rid of it, kind of like decaffeinating coffee."

For example, in collaboration with Scott Hemby, PhD, at High Point University, they investigated whether mitragynine and 7-hydroxymitragynine would be like morphine and self-administered by rats by trained to press a lever to receive it, a measure of addictive potential. However, this work has not yet been submitted for peer-reviewed publication because McCurdy thinks they'll need other studies to publish a complete report. Although the university issued a press release on this work, regulators and the scientific community do not regard unpublished work as definitive.

Survey of kratom users

At the same time, his laboratory was funded for another project on salvinorin A, a hallucinogenic kappa opioid agonist that was discovered from the Salvia divinorum plant. He was collaborating with Boyer, an emergency physician, director of UMass medical toxicology and opioid treatment specialist, and got to talking about kratom. Boyer got onto drug use chat rooms and did a nonscientific survey with opioid addicts where he polled users about kratom, whether they've used it, what for and what kind of effects they experienced when stopping it.

This work was published, in 2008 in the journal Addiction, with the conclusion, "One striking finding of this report is the extent to which kratom attenuates potentially severe opioid withdrawal, yet cessation of kratom administration itself appears to be associated with modest abstinence symptoms."

The potential for kratom itself to have addictive qualities as an opioid has been a major scientific question, and one for regulators. The problem is that we are currently at the anecdote stage.

"Is it addictive? It may be, slightly. But without any control or standardization of products that are out there, it's hard to say what people are using," adds McCurdy.

Among the 200 or so messages I've received this month for users touting the benefits of kratom, I've also received four notes from users, or partners of users, who've become addicted to kratom. A Reddit discussion board, r/quittingkratom, is also dedicated for users to discuss their difficulties in discontinuing use of the herbal product. A systematic risk-benefit study of verified, unadulterated kratom products is certainly warranted.

Kratom as a "lifesaver"

But McCurdy also says that he sees significant medical potential in kratom. "Over the years, I've gotten dozens, probably hundreds, of emails from people saying what a lifesaver kratom has been for them to not feel drugged but still use something that helps their chronic pain," says McCurdy. "So we've been really encouraged to keep pursuing the science because we don't fully know all the science behind the plant. That's been our mission: to see if there's medical benefit from it. There certainly appears to be medical benefit from the number of people who are using it for that."

McCurdy and Boyer already suspected as early as 2008 that kratom might also have utility in treating other forms of substance dependence and filed a U.S. patent application for those uses. That application is still pending.

Concern over kratom adulteration, not abuse

While human clinical trials are certainly necessary to systematically investigate kratom's full medical potential, McCurdy does have some reservations over the herb's sale as a dietary supplement.

"I'm not totally opposed to it being regulated in some aspects because we've come across samples where we've been contacted by emergency rooms, in one case where a baby was born in what was clearly opioid withdrawal," says McCurdy. "The mother insisted that she had not been using any opioids during her pregnancy. So we got the kratom sample she was taking and found it was laced with morphine and oxycodone."

Adulteration of herbal supplements has been a perennial problem in the dietary supplement market. Weight loss supplements and "men's wellness" products have been repeatedly found by FDA to be adulterated with current or former prescription weight loss drugs and erectile dysfunction drugs, respectively. So common are these episodes that the agency maintains a testing program for these products.

But weight loss and men's health supplements haven't been criminalized. What does McCurdy see as the middle ground?

"From a regulatory standpoint, I'd love to see some standardization and assurance that there's not adulteration. I've got kids. I don't want to see my kids using it. I'd like to see it out of gas stations until we see what this is all about."

So I asked McCurdy if placing kratom compounds on Schedule I was the right way to go about such regulation.

"I don't think so," says McCurdy. "That's been one thing we've been worried about for a long time. All you have to do is look at marijuana and see the problem about getting it deregulated and doing the necessary medical studies." This summer, the DEA rejected a petition to downschedule marijuana from Schedule I.

"I hate to see kratom without the science behind it suddenly be thrown in the same place as bath salts and LSD and other drugs with far more danger than what we see with kratom," says McCurdy.

David Kroll, PhD, is a former academic pharmacologist and educator. For more health and pharmaceutical news and commentary, follow him on Facebook, Twitter @DavidKroll or here at Forbes.

I'm a pharmacologist, freelance science and medicine writer, educator, and speaker with a passion for public understanding of science and medicine. I report on all things pharmaceutical and scientific from Durham, North Carolina, home of the Research Triangle Park.